Rearrangements of the c-myc oncogene are present in 15% of primary human multiple myeloma tumors

Rearrangements of the c-myc oncogene have been found in most plasmacytomas induced in mice and human myeloma cell lines (HMCLs) analyzed so far. Howev er, neither induced mouse plasmacytomas nor HMCLs represent relevant models for human multiple myeloma (MM). To evaluate the incidence of c-myc rearra ngements in human plasma cell dyscrasias, sets of probes were generated to allow direct assessment of c-myc translocations on interphase plasma cells by using fluorescence in situ hybridization. After validation of these prob es, a large cohort of patients with either newly diagnosed MM (n = 529), re lapsed MM (n = 58), primary plasma cell leukemia (PCL; in = 23), monoclonal gammopathy of undetermined significance (n = 65), or smoldering MM (n = 24 ) were analyzed. C-myc rearrangements were identified in 15% of patients wi th MM or primary PCL, independently of the stage of the disease (ie, diagno sis or relapse and MM or primary PCL). Analysis of the 2 main translocation s observed on karyotyping, le, t(8;14) and t(8;22), revealed that these spe cific translocations represented only 25% (23 of 91) of c-myc rearrangement s. c-myc rearrangements were then correlated with several other patients' c haracteristics: illegitimate IgH recombinations, chromosome 13 deletions, a nd serum beta2-microglobulin levels. The only significant correlation was w ith a high beta2-microglobulin level (P = .002), although a trend for assoc iation with t(4;14) was observed (P = .08). Thus, c-myc rearrangement analy sis in patients with MM revealed a strikingly lower incidence than that in HMCLs and plasmacytomas induced In mice, indicating that data obtained with these models cannot be directly extrapolated to human MM. (C) 2001 by The American Society of Hematology.